Indigo Carmine (Blue 2 Dye): Safety, Uses, and Side Effects

Indigo Carmine (Blue 2 Dye) is a dark blue dye used to enhance the color of some foods, beverages, cosmetics, clothing, supplements, and medications. While it may improve the appearance of these and other consumer products and is often cheaper than natural alternatives, Blue 2 Dye has been associated with several health concerns, particularly in animal studies.

This article explores the names and uses of Blue 2 Dye, which products contain this common food colorant, its potential health risks, and considerations regarding its safety for human consumption. 

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Background on Indigo Carmine (Blue 2 Dye)

Indigo Carmine (Blue 2 Dye) was chemically developed to improve the blue color of certain consumer products.

History and Development

Blue 2 Dye, also called Indigo Carmine, FD&C Blue No. 2, and Indigotine, is an indigo or dark blue powder (organic sodium salt) developed by condensing the acid form of indigo carmine with sodium hydroxide. 

Chemical Composition and Formula

The chemical composition of Indigo Carmine (Blue 2 Dye) is:

•  Disodium;2-(3-hydroxy-5-sulfonato-1H-indol-2-yl)-3-oxoindole-5-sulfonate

Its molecular formula is C16H8N2Na2O8S2.

Regulatory Status and Approval by Health Authorities

Blue 2 Dye is approved by the United States Food and Drug Administration (FDA), European Food Safety Authority (EFSA), and Joint FAO/WHO Expert Committee on Food Additives (JECFA) in amounts based on kilograms of body weight. 

Uses of Indigo Carmine (Blue 2 Dye)

The following are examples of uses of Indigo Carmine (Blue 2 Dye).

Common Applications in Food Products

Foods and beverages that may contain Indigo Carmine include:

• Breakfast cereals
• Sports drinks
• Energy drinks
• Other beverages 
• Ice creams
• Sorbets
• Dairy foods
• M&Ms
• Skittles
• Other candies
• Snack foods
• Baked goods
• Dessert powders
• Confectionary products
• Sausages
• Maraschino cherries
• Pet foods

If a highly processed food is blue in color, chances are it contains Blue 2, Blue 1, or other blue food dyes. 

Use in Pharmaceuticals and Medical Diagnostics

Uses of Blue 2 Dye in pharmaceuticals include the following medications:

• Cyclobenzaprine hydrochloride 
• Tamsulosin hydrochloride
• Viagra
• Doxycycline hyclate
• Morphine sulfate extended release
• Oxycodone hydrochloride 
• Sertraline hydrochloride 
• Alprazolam 
• Amphetamine and dextroamphetamine extended release
• Clonazepam 

Blue 2 Dye is found in prenatal vitamins, children's vitamins, children’s pain relievers, and children’s allergy tablets. 

Indigo Carmine is also used in milk testing to detect chlorates and nitrates and renal function testing to detect chlorates and bitrates. It’s sometimes used as a reagent for kidney function tests during ureteral catheterization and cystoscopies. 

Cosmetic and Other Uses

Cosmetic and other uses for Indigo Carmine (Blue 2 Dye) include:

• Hair dyes
• Fragrances
• Soaps 
• Bubble baths
• Eye liners
• Hair styling aids
• Shampoos
• Some surgical sutures
• Nylon
• Denim

Blue 2 is used as a dye to color some types of clothing. 

Comparison With Other Similar Dyes

Blue 1 Dye is a synthetic dye similar to Blue 2. However, Blue 1 is lighter, slightly greenish blue in color, while Blue 2 is darker blue or indigo. Both Blue 1 and Blue 2 are used to color drinks, foods, vitamins, medications, cosmetics, and other common consumer products. 

But unlike Blue 2, Blue 1 Dye is made of petroleum. Blue 2 is a synthetic version of plant-based indigo dye. 

Blue 1 also has a different chemical composition: Disodium;2-[[4-[ethyl-[(3-sulfonatophenyl)methyl]amino]phenyl]-[4-[ethyl-[(3-sulfonatophenyl)methyl]azaniumylidene]cyclohexa-2,5-dien-1-ylidene]methyl]benzenesulfonate.

Regulatory differences between these two blues also exist. Regulatory agency guidelines for Blue 1 are as follows:

• Blue 1 FDA: 0-12 milligrams per kilogram of body weight daily
• Blue 1 EFSA: 0-12.5 milligrams per kilogram of body weight daily
• Blue 1 JECFA: 0-6 milligrams per kilogram of body weight daily

These regulations allow lower levels of Blue 2 than Blue 1.

Safety of Indigo Carmine (Blue 2 Dye)

While well-known regulatory agencies deem Blue 2 Dye safe in recommended amounts, potential health concerns have been reported.

Overview of Safety Assessments by Regulatory Agencies

Food dye safety assessments by regulatory agencies are based mainly on animal studies since there are very few human studies. While the FDA, EFSA, and JECFA have approved Blue 2 Dye for use in foods and other consumer products, updated guidelines may become available as new research emerges. 

Acceptable Daily Intake (ADI) levels

Accepted daily intakes (ADIs) for Indigo Carmine (Blue 2 Dye) include:

• FDA: 0-2.5 milligrams per kilogram of body weight daily
• EFSA: 0-5 milligrams per kilogram of body weight daily
• JECFA: 0-5 milligrams per kilogram of body weight daily

These are the amounts of Blue 2 per kilogram of body weight daily deemed safe for consumption by these agencies.

Metabolism and Excretion in the Human Body

While human studies on Blue 2 metabolism are lacking, research on Blue 2 Dye metabolism in rats shows that this dye and its metabolites are mainly excreted in feces, with small amounts lost in the urine. The researchers concluded that much of the ingested Blue 2 Dye was not absorbed by rats.

Side Effects and Health Risks

Side effects and health risks are associated with Indigo Carmine (Blue 2 Dye). 

Potential Side Effects and Adverse Reactions

Blue 2, as well as many other synthetic food dyes, may cause allergic reactions or gastrointestinal issues in people who are sensitive to artificial food colorings. Bronchoconstriction, itching skin, and even anaphylaxis in rare cases are examples of allergic reactions observed after consuming products containing Blue 2 Dye.

A human case study reported low blood pressure, low oxygen, wheezing, and a life-threatening anaphylactic reaction after an indigo carmine injection for a ureter evaluation.

Another study suggests that Indigo Carmine may be toxic for humans and could lead to low blood pressure, high blood pressure, skin irritation, or gastrointestinal (GI) disorders. 

Another study indicated that Indigo Carmine has the potential to cause vomiting, nausea, diarrhea, and skin irritation. 

Long-Term Health Risks

Indigo Carmine may also be linked to longer-term health risks. Synthetic food dyes are associated with neurobehavioral problems in children, such as potentially worsening attention-deficit/hyperactivity disorder (ADHD) symptoms. 

The Center for Science in the Public Interest suggests that neurobehavioral effects that may become more severe in children because of food dyes include:

• Inattentiveness
• Hyperactivity
• Restlessness
• Sleeplessness
• Aggression
• Irritability

Furthermore, blue dyes appear to have toxic effects, including potential carcinogenicity (cancer-causing) concerns. Therefore, some researchers suggest considering natural dyes as alternatives to synthetic blue food dyes (blue 1 and Blue 2) with natural dyes.

The Center for Science in the Public Interest suggests that Blue 2 may not be safe because of the statistically significant incidence of tumors, including brain tumors, in rats. 

The Environmental Working Group confirms that Blue 2 Dye may cause bladder and brain tumors in rats. This organization is concerned about the potential health effects of Blue Dye 2 and other synthetic dyes used to color foods. 

However, human studies associated with Indigo Carmine’s effects on cancer in humans are lacking. 

Vulnerable Populations and Individual Sensitivity

Vulnerable populations for food dye sensitivity and allergic reactions may include children, babies, pregnant women, and individuals with food dye sensitivities. However, the FDA hasn’t established specific safe ADIs for children, pregnant women, and other sensitive population groups. 

Studies and Research on Indigo Carmine (Blue 2 Dye)

Many studies using Indigo Carmine involve animals, though some human studies have been conducted. 

Summary of Key Scientific Studies

Key studies suggest that Indigo Carmine may be toxic for humans and could lead to high blood pressure, low blood pressure, skin irritation, allergic reactions, gastrointestinal disorders, and other potentially concerning health effects. 

Findings on Toxicity and Carcinogenicity

Studies show that Blue Dye 2 is linked to brain tumors in rats. The researchers suggest that because of this (while human studies are lacking), Indigo Carmine may not be safe for human consumption. 

Research on Behavioral Effects

Studies examining the effects of Indigo Carmine on behavior in children found that synthetic food dyes appear to increase inattention and hyperactivity in children with ADHD and kids without an ADHD diagnosis. 

Alternatives to Indigo Carmine (Blue 2 Dye)

Natural colorants may have distinct advantages over synthetic food dyes when it comes to human health and well-being.

Natural Alternatives and Their Benefits

Natural colorants with the potential to replace Indigo Carmine (Blue 2 Dye) or other synthetic dyes include:

• Phycocyanin: natural colorants sourced from algae.
• Natural indigo: water-soluble glucoside indicant in plants.
• Anthocyanins (E163): found in berries, grapes, other fruits, radishes, cabbage, potatoes, and other vegetables.
• Gardenia blue: present in G. jasminoides fruits that grow in forests in Japan, Taiwan, Vietnam, and China. 

Researchers suggest that anthocyanins and genipin (obtained from G. jasminoides fruits) are examples of natural blue food dyes associated with health benefits – such as supporting a healthy heart, and cancer with neuroprotective, anti-diabetic, anti-inflammatory properties. 

Examples of FDA-approved natural blue colorants for foods are grape skin and grape extracts (anthocyanins).

However, the downside for food manufacturers is that natural colorants are often more expensive and may be less stable than synthetic food dyes.

Comparison of Safety Profiles

Researchers have expressed safety concerns for individuals who ingest Blue 2 or similar synthetic dyes, including Blue 1. That’s why there’s a strong interest in creating natural alternatives to synthetic blue food colorants. 

Industry Trends Towards Natural Coloring Agents

Food manufacturers and other industries are trending toward natural colorants over synthetic dyes. Emerging natural dyes, including substances found in red cabbage and other fruits and vegetables, show promising results to replace Blue 2 Dye and other artificial dyes. New regulations and research may result because of these new developments.

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Key Takeaways

• Indigo Carmine (Blue 2 Dye) is a synthetic blue colorant commonly used in foods, drinks, supplements, medicines, clothing, cosmetic products, and pet foods. 
• However, potential health concerns exist when consuming large amounts of Blue 2. Examples include cancer, hyperactivity in children, GI issues, and allergic reactions.
• The FDA, EFSA, and JECFA deem Indigo Carmine (Blue 2 Dye) safe in limited amounts. However, some adults and children who eat large amounts of highly processed, brightly colored foods may exceed these levels. 
• Some consumer advocacy groups recommend Indigo Carmine (Blue 2 Dye) and other synthetic dyes be removed from the food supply due to potential health concerns.
• To avoid potential health risks associated with Blue 2 Dye, consider limiting or avoiding foods containing this artificial colorant (read the ingredient label or choose organic options instead). Consider products labeled dye-free or those using natural blue alternatives.